Abstract

To study the magnitude of the complication of catheter associated
right atrial thrombus (CRAT) in patients with tunnelled central venous
hemodialysis catheters (THC) for maintenance hemodialysis (MHD).

A retrospective study was conducted among patients
with end stage kidney disease (ESKD) with THC for MHD who had undergone
screening for CRAT with a 2D-echo (2DE) just before removal of the THC. The
occurrence of CRAT and other clinical parameters were documented in these
patients.

A total of 28 patients (mean [SD] age 51 [15.2] years; females 17 [60.7%])
were included in the study. CRAT was observed in 5 (17.9%) patients. There was
no difference in mean age in patients with or without thrombus (48±13.02 vs
51.61 ± 15.78 years; p = 0.61). History of diabetes and hypertension was present
in 2 and all 5 patients respectively. There was no significant difference in the
period the THC was in place in patients with or without CRAT (13±7.8 months vs
10.57±5.66 months; p = 0.54). There was no association between catheter related
blood stream infection (CRBSI) and CRAT (p= 0.29)

The incidence of CRAT in patients with THC for MHD was 17.9%.
Patients with THC for MHD should be examined for presence of CRAT before
removal of THC to prevent fatal pulmonary thromboembolism.

Introduction

Patients suffering from end stage
kidney disease (ESKD) need renal
replacement therapy for life sustenance.
Renal replacement therapy includes
three modalities namely, hemodialysis,
peritoneal dialysis and kidney
transplantation. Hemodialysis is the
most frequently used renal replacement
modality in India and elsewhere. An
appropriate vascular access is necessary
to carry out hemodialysis. Of the
three types of vascular accesses used
frequently, central venous dialysis
catheters, arteriovenous grafts and
arteriovenous fistula (AVF), the latter
is the most appropriate option.1 It is
recommended to create an AVF when
the estimated glomerular filtration
rate (eGFR) falls below 25 ml/min, well
before MHD is needed.2 However, most
patients are not compliant and need a central venous hemodialysis catheter
to commence hemodialysis. Many
other patients present late needing
immediate dialysis, in which situation
a central venous hemodialysis catheter
is the only available option. Hence
majority of patients initiate dialysis
with a central venous hemodialysis
catheter.3

Hemodialysis catheters are either
non – tunnelled or tunnelled, the latter
being preferred both by clinicians and
patients. THCs are superior to non –
tunnelled catheters as the incidence of
venous thrombosis and stenosis is less
and the tunnelling and cuff reduce the
chances of CRBSI. These properties ensure that they can be retained in
situ for a prolonged period.4 However,
they are more expensive and trained
personnel are needed to insert them
under fluoroscopy.

The frequency of insertion of THC
has increased considerably in India.
When compared to an AVF, THC have
higher risk of infection, thrombosis and
catheter related dysfunctions resulting
in higher morbidity and mortality.5,
6 In view of these observations THC
should only be used as a bridge till
AVF matures and can be accessed for
hemodialysis.7

THC may lead to asymptomatic
catheter - associated right atrial
thrombus (CRAT) which may contribute
to increased morbidity and mortality.8
The incidence of CRAT has been
reported to be 18 % in patients with
THC.9 Removal of THC in patients
with a CRAT may lead to pulmonary
embolism and death.10 In our centre
we documented a case of CRAT
diagnosed as an incidental finding on
2D echocardiography (2DE). Following
this observation all patients in our unit
are screened for CRAT before removal
of THC. There has been only one study
reported, looking at the incidence of
CRAT in patients with THC. Currently
there are no published data from India
on the incidence of CRAT in patients
with THC.

Objectives

To study the magnitude of the
complication of CRAT in patients with
THC for MHD in ESKD patients and to
understand the factors associated with CRAT formation.

Materials and Methods

This is a retrospective, observational
study conducted at Bombay Hospital
Institute of Medical Sciences, a tertiary
care hospital in Mumbai. ESKD patients
on MHD having a THC in situ between
August 2017 to July 2018 who underwent
2DE before removal of the THC as a part
of the unit protocol, were included in
the study. Patients who died or were
lost to follow-up were excluded from
the study. Patients with acute kidney
injury were excluded from the study.

The THCs were inserted by
the same experienced critical care
consultant under ultrasound guidance.
The procedure was done in the
interventional radiology laboratory. All
THCs were Palindrome® manufactured
by Covidien (now Medtronics). The tip
was placed in the mid right atrium in 26
patients and at the junction of superior
venacava and right atrium in 2 patients.

The 2DE studies were carried out by
the same experienced cardiologist using
Philips EPIQ 7C machine. Assessments
were performed in apical, parasternal
and subcostal views in accordance with
the current recommendations. When
CRAT was identified, its size, mobility,
echogenicity and attachment to the THC were assessed.

The frequency of occurrence of
CRAT was documented along with
the duration of THC in situ, use of
antiplatelets or anticoagulants, use of
erythropoietin, history of thrombosis
of previous non-tunnelled dialysis
catheter or AVF, heparin usage, any
variation in heparin locks, demographic
characteristics, comorbid conditions,
cause of ESKD, type and frequency of
dialysis, blood pump speeds and blood
tests (haemoglobin, complete blood
count and complete biochemistry) were
recorded. Any complications related to
THC insertion were recorded.

This study protocol was approved
by the hospital’s ethics committee.

Statistical Methods

A t-test was performed for
comparing the means of 2 set of
continuous data. Fisher’s exact test
and Pearson Chi-Square tests for
comparing two categorical datasets
were used. Variables were expressed
as “mean ± standard deviation”, while
categorical variables were expressed as
number and percentage. R programming
language was used for doing these
statistical tests. To check if CRAT
was linked to some parameters and if
there were any nonlinear relationship
between the various variables and
CRAT, classification and regression
trees method was used. A p level less
than 0.05 was considered significant in
the statistical analysis.

Results

A total of 28 patients were included in the study. The baseline demographic
characteristics and the laboratory
parameters of overall study population
are shown in Tables 1 and 2 respectively.

The mean (SD) age of overall patient
population was 51 (15.2) years. The
study population was dominated
by females (17[60.7%]). History of
hypertension was more common than
history of diabetes in study population
(78.6% vs 35.7%). Three patients
(10.71%) had ischemic heart disease.

Viral serology was negative in all
patients except one who had presence
of HCV antibodies. Another patient
showed presence of antinuclear
antibodies.

CRAT was observed in 5 (17.9%) of the
28 studied patients. The demographic
characteristics, cause of CKD, history
of diabetes and hypertension and
duration of THC are shown in Table
3. The characteristics of CRAT on 2DE
study are shown in Table 4.

Out of the 5 patients, 3 were males
and 2 were females. The mean age in
patients with or without thrombus
was 48±13.02 and 51.61 ± 15.78 years,
respectively, with no significant
difference (p = 0.61).

The range of duration of hemodialysis
during screening ranged from 10
months to 72 months. The duration
of THC in these patients ranged from
8 months to 24 months. The mean
duration of THC in patients with or
without CRAT was 13±7.8 months
and 10.57±5.66 months. There was no
significant difference in duration of
THC between the two groups (p = 0.54).

Two patients had history of diabetes
whereas history of hypertension
was present in all 5 patients. Of the
10 diabetic patients, 2 (20%) had
CRAT, while 3 of the 18 non-diabetic
individuals (16.7%) had CRAT, with
no significant difference between
the groups (p = 1.0). CRAT formation
was detected in 22.7% (5/22) of the
hypertensive patients and in none of the non-hypertensive patients (p = 0.55).

A total of 10 (35.7%) patients in the
study were on antiplatelets. All patients
were receiving erythropoietin. None
of the patients were on any form of
anticoagulation therapy. All patients
received fractionated heparin during
hemodialysis. All patients received
thrice a week hemodialysis. Both
ports of the THC were locked with
unfractionated heparin solution in all
patients.

Discussion

A large proportion of patients
with ESKD needs THC for initiating
MHD as they present late with ESKD
needing immediate dialysis or they
may have refused an AVF earlier.
Some patients need THC because of
secondary AVF failure.11 In this study
12(42.8%) patients had THC as their
first vascular access, 8(28.5%) had it
after an initial non-tunnelled dialysis
catheter and 8 (28.5%) had THC placed
because of secondary AVF failure.

THC placement procedure may be
complicated by arterial punctures,
pseudoaneurysm , hematoma ,
air embolism , pneumothorax
and malposition.12 None of these
complications were encountered in the
current study, as the procedure was
performed by an experienced operator,
under ultrasound and fluoroscopic
guidance in the interventional radiology
laboratory.13

Other complications seen with THC
include CRBSI, catheter malfunctioning,
venous thrombosis and stenosis.14 In the
current study, 3 THCs were removed
because of malfunctioning, 4 because
of CRBSI, 1 following successful live
related kidney transplantation and
19 following AVF maturation and 1
patient died with THC in situ. None of
the patients in the study had venous
thrombosis. Six patients (21.4%) out of
the 28 studied had CRBSI. Four of these
had their THCs removed, 2 of whom
had CRAT. Two patients were treated
appropriately with antibiotics and did
not require removal of THC for CRBSI.
These two were removed later after AVF
maturation. 33.3% (2/6) patients with
CRBSI had CRAT. This association was
not statistically significant (p = 0.2855).
Dilek et al too in their study did not
find any correlation between CRBSI
and CRAT.9

CRAT is a less frequently observed complication but has serious lifethreatening
implications.10,15 In the
current study, CRAT was observed
in 17.8% (5/28). There is limited data
regarding the frequency of occurrence
of CRAT. In the only study looking at
the incidence of CRAT, the incidence
was found to be 18% (9/50).9 Since CRAT
is largely asymptomatic, it generally
goes undetected in clinical practice
and hence the incidence of this serious
complication is underestimated or may
go undetected. CRAT was detected by
2DE in most published data.9 Magnetic
resonance imaging and computerised
tomography scan have been used to
detect intracardiac thrombi.8 But 2DE
is freely available, is non-invasive with
no risk of radiation and is a cheaper
screening tool prior to THC removal.
The sensitivity and specificity of 82.2%
and 95.3% respectively of 2DE in
detecting intracardiac masses ensures
its efficacy.16

What predisposes patients to
develop CRAT is unclear. The duration
of the THC in situ does not seem to be
a risk factor for CRAT. In the current
study the duration of THC in patients
with or without CRAT was 13.0 ± 7.81
and 10.56 ±5.66 months respectively,
and this was not significant (p = 0.5384).
This is comparable to outcomes in
previously published data.9 The age,
BMI, cause of kidney disease, use of
antiplatelets, haemoglobin values,
history of secondary AVF failure due
to thrombosis, low ejection fraction or
diastolic dysfunction had no relation
to CRAT formation. All patients were
on similar protocol of unfractionated
heparin during dialysis. All patients
received erythropoietin for the
management of anaemia. All patients
were on thrice weekly hemodialysis.
In the current study, CRAT was found
in 2 females (2/5). In two other studies
there were more females in the patient
population presenting with CRAT.8,9 All
patients with CRAT were hypertensives,
two patients had diabetes mellitus and
none had ischemic heart disease.

It has been shown that patients with
chronic kidney disease are at an increased
risk of venous thromboembolism
due to a host of factors.17 Mechanical
irritation of the right atrial free wall
by THC tip or high blood flows may
lead to endothelial damage which
may activate coagulation cascade,
platelet aggregation and thrombi
formation.1 There was less central venous thrombosis when THC tips were
placed in the right atrium as compared
to tips placed in the superior vena
cava in one study.18 Kidney Disease
Outcomes Quality Initiative (KDOQI)
guidelines recommend that the THC
tip should be positioned, with the aid
of fluoroscopy, in the right atrium or
at the junction of superior venacava
and right atrium, to ensure adequate
blood flow and lesser incidence of
THC dysfunction.19 In the current
study 26 patients had their THC tips
positioned in the mid right atrium and
2 at the junction of superior vena cava
and right atrium. Right jugular vein
was the preferred site of cannulation
and was used in 22 patients while in
the remaining 6, left jugular was used.
All the five patients with CRAT had
right jugular THC. Since the study
population was small, a correlation
could not be made.

Studies looking at prevention of
CRAT in haemodialysis patients using
anticoagulation and antiplatelets
have not shown any benefit of these
strategies . 20 KDOQI guidelines
recommend not using antiplatelets
and anticoagulation for prevention of
CRAT and venous thrombosis, as this
increases the risk of bleeding.

The treatment options include
anticoagulation , endovascular
techniques and surgery. Anticoagulants
have been proposed as the first -
line treatment of CRAT provided
there are no contraindications.8 If
anticoagulation is used, 2DE at regular
intervals should monitor progress.21
Endovascular techniques may be
considered if facilities are available in
the institute. Surgical thrombectomy
can be considered in cases where the
thrombus is more than 6 cms.8 Both
endovascular and surgical techniques
carry a certain element of risk leading
to serious complications.8

In this study, of the five patients
with CRAT three were treated with
anticoagulation. These three patients
had large CRAT measuring 4 × 2 cms,
3 × 3 cms and 3.5 × 2.5 cms. One of the
patients died of an unrelated cause.
Complete resolution of the CRAT in
the other two patients occurred after
4 months. This ensured that the risk
of pulmonary thromboembolism was
mitigated while removing the THC.
The remaining two of the five patients
with CRAT, needed removal of the THC
because of infections. One had fungal sepsis requiring immediate removal of
THC, other had methicillin sensitive
staphylococcus aureus infect ion
which did not respond to appropriate
antibiotics. Before removal, an informed
consent was obtained from the patients
and their families, explaining the
risk of pulmonary thromboembolism
and its consequences. Subsequently
none of these two patients developed
pulmonary thromboembolism and
both recovered from the sepsis. The
CRAT was smaller in these two patients
measuring 1.5 × 1.2 cms and 1.8 × 2
cms. It is possible that infected CRAT
is probably more adherent to the THC,
which needs to be proved.

In a retrospective analysis of
reported cases the overall mortality
was18.3% (13/71), significant predictors
being advanced age, presence of
complications and non-removal of the
THC.8 In another retrospective study
looking at the incidence of CRAT, a
mortality of 44.4% (4/9) over a 2 years
follow-up was reported.9 The current
study data did not show any significant
relationship between the presence of
CRAT and mortality. Out of the five
patients with CRAT, one died due to
an unrelated cause.

Although all efforts are made to
counsel patients with chronic kidney
disease to have an early AVF placed
when the eGFR is 25ml/min, most
patients do not comply resulting in the
need for THC to initiate hemodialysis.
CRAT was found in 17.8% (5/28) of
patients in the current study. With the
more widespread usage of THC in recent
years, an increased number of CRAT
may be encountered. Since the risk of
fatal pulmonary thromboembolism is
high during the removal of the THC,
mandatory screening with a 2DE before
removal may reduce fatal outcomes.
The frequency of occurrence of this complication and being primarily
asymptomatic but potentially life
threatening, screening for CRAT once
in two months could be beneficial in
early diagnosis and possible therapy
with anticoagulation with finally
removal of THC. A larger prospective
observational study is needed to
validate this.

Conclusion

The frequency of CRAT in patients
with THC was 17.9% in the current study.
There is limited data about incidence of
CRAT in Indian patients on MHD. The
present study provides insights into
the possibility of asymptomatic CRAT
in patients with THC used for MHD.
The results may provide guidance in
ensuring screening for asymptomatic
CRAT with a 2DE before removal of
THC thus reducing the risk of serious
pulmonary thromboembolism.

Declaration of Interest

The authors report no conflicts
of interest. The authors alone are
responsible for the content and writing
of the paper.

United States Renal Data System. 2016 USRDS Annual Data
Report: Epidemiology of Kidney Disease in the United States.
National Institutes of Health. National Institute of Diabetes
and Digestive and Kidney Disease, Bethesda, MD; 2016.
Available from: https://www.usrds.org/adr.aspx. [Internet].
2016.

United States Renal Data System. 2016 USRDS Annual Data
Report: Epidemiology of Kidney Disease in the United States.
National Institutes of Health. National Institute of Diabetes
and Digestive and Kidney Disease, Bethesda, MD; 2016.
Available from: https://www.usrds.org/adr.aspx.